Advances in Hematology最新文献

Universal in the United States (US) since 2006, newborn screening (NBS) programs for sickle cell disease (SCD) allow for early identification of the disease and, as an unintentional byproduct, identification of sickle cell trait (SCT). Unlike other carrier states, SCT is highly prevalent and is found in nearly 3 million Americans, which results in important reproductive implications. Currently, all NBS programs in the US are responsible for their own policies regarding SCT notification, and little is known about how SCT notification practices are performed and how these practices vary across NBS programs. We surveyed NBS programs personnel in all 50 states, the District of Columbia, and the US' territories of Puerto Rico and Guam (n = 53) using an electronic survey. There was a 100% response rate. All NBS programs (100%) provide notification of SCT status to either a pediatrician or parent: 49% notify the pediatrician only, 45% notify both the pediatrician and parent, and 6% notify the parent only. A total of 98% of NBS programs retain electronic records of SCT status, but only 38% can be directly accessed by pediatricians/primary care doctors. No state operates a publicly available database that allows individuals to access their own records. Only one state provides renotification at reproductive age. In conclusion, there is wide variability in NBS practices for SCT notification. This study demonstrates a need for national guidelines to standardize SCT notification across the US to ensure effective notification and counseling for SCT.

Objective: The present study aimed to evaluate for the first time, the early molecular response (EMR) to imatinib at 3 months for patients with chronic myeloid leukemia and to determine the predictive factors that influence poor outcome and response. Methods: 60 newly diagnosed CML patients were enrolled from May 2018 to June 2023. They received imatinib and prospectively underwent a molecular evaluation. Their EMR was assessed using a RT-qPCR method and expressed as the BCR::ABL1 IS transcript level at 3 months. Potential factors impacting the EMR were identified using the Cox proportional hazard regression models. The effects of an EMR on the cumulative incidence of a deep molecular response (DMR) were also evaluated. Results: Out of the 60 CML patients recruited, 29 (48%) achieved an optimal response with TKI therapy after 3 months. The cumulative rate of molecular response was 16 (36%) for a major molecular response (MMR), 10 (23%) for MR4, 8 (18%) for MR4.5, and 6 (14%) for MR5, while 4 (9%) showed indetectable transcript. In addition, as 26 (90%) of patients with optimal response at 3 months showed a DMR, we determined that an optimal response to TKI at 3 months was significantly correlated with a DMR. We also identified through multivariate analysis that seven independent risk factors significantly influenced an EMR to TKI. These factors included male, late diagnosis, advanced performance status, the presence of splenomegaly, high-ELTS risk groups, a BCR::ABL1 domain mutation, and complete hematologic response after more than 30 days. Conclusion: Our study demonstrates that an EMR at 3 months has a predictive value for a DMR. In addition, a MMR and a DMR can be predicted using a combination of parameters that either have a significant impact on the optimal response, or that can serve as prognostic indicators for molecular response, especially in low-income countries, where molecular assessment and monitoring are not available or possible.

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or α-thalassemia. We hypothesize that increased transferrin saturation is associated with increased mean cellular hemoglobin concentration (MCHC) which in turn is associated with decreased red cell counts and worsening anemia. To investigate this hypothesis, we examined the relationships between transferrin saturation and MCHC with each of the parameters that define MCHC in sickle patients (HbSS without α-thalassemia) and healthy volunteers (HVs). Results indicate that transferrin saturation and MCHC are positively correlated with each other in sickle patients and HV. In patients with SCD, MCHC and transferrin saturation are negatively correlated with RBC count and are not correlated with hemoglobin, whereas each is positively associated with HV. Transferrin saturation and MCHC are each positively correlated with the hemolysis marker, lactate dehydrogenase. These observations support a model where increased transferrin saturation contributes to higher intracellular HbS concentrations with subsequent increases in sickling and hemolysis in sickle patients, suggesting that pharmacologic approaches to decrease serum iron may provide a therapeutic approach for patients with SCD. Trial Registration: This study was registered with ClinicalTrials.gov identifiers: NCT00011648, NCT00081523, and NCT04817670.

Background: Hydroxyurea (HU) is a disease-modifying therapy with significant clinical and laboratory efficacy among individuals living with sickle cell anaemia (SCA). This is evident through increased fetal haemoglobin, higher packed cell volume, improved red cell hydration, reduced leukocytes, and platelet function. The effect on the coagulation pathway and pathophysiologic mechanism remains unclear, especially in children living with SCA. This study evaluated the coagulation profile using D-dimer and thrombin antithrombin complex (TAT) in children with SCA. Methods: The cross-sectional study was conducted over three months at LUTH among 80 children living with SCA in steady state aged 2-18 years (40 HU exposed and 40 HU naïve, respectively). Blood samples were assayed for D-dimer, TAT, and complete blood count. Descriptive analysis such as mean and standard deviation for normally distributed variables or median and interquartile range for skewed data were used to summarize continuous variables, while proportion or percentages for categorical variables. Univariate analysis and bivariate analysis were done and statistical significance was set at p < 0.05. Results: The mean age (±SD) of study participants in both groups was 11.35 (±4.6 years). D-dimer levels (23.27 ng/mL) and TAT (29.79 pg/mL) were significantly lower among HU exposed compared to HU naïve children (62.73 ng/mL and 109.34 pg/mL, respectively) p < 0.001. There was a negative correlation between D-dimer and TAT with the duration of HU use (r = -0.499, p=0.001, and r = -0.401, p=0.010), respectively. There was a positive correlation between D-dimer and TAT with total WBC (r = 0.368, p=0.019, and r = 0.385, p=0.014, respectively) among the HU naïve participants and a negative correlation between D-dimer and TAT with haemoglobin level (r = -0.303, p=0.047, and r = -0.311, p=0.041, respectively) among HU exposed children. Conclusion: HU modulates the D-dimer and TAT levels of children living with SCA toward the normal reference range, thus reducing the risk of hypercoagulability and associated sequelae. Therefore, continuous advocacy for HU use should entail close monitoring of adverse effects.

Lymphoma is the sixth most prevalent cancer globally. Non-Hodgkin's lymphomas are the majority group of lymphomas, with B cells accounting for approximately 95% of these lymphomas. A key feature of B-cell lymphoma is the functional perturbations of essential biological pathways caused by genetic aberrations. These lead to atypical gene expression, providing cells with a selective growth advantage. Molecular analysis reveals that each lymphoma subtype has unique molecular mutations, which pose challenges in disease management and treatment. Substantial efforts over the last decade have led to the integration of this information into clinical applications, resulting in crucial insights into clinical diagnosis and targeted therapies. However, with the growing need for more effective medication development, we anticipate a deeper understanding of signaling pathways and their interactions to emerge. This review aims to demonstrate how the BCR, specific signaling pathways like PI3K/AKT/mTOR, NF-kB, and JAK/STAT are diverse in common types of B-cell lymphoma. Furthermore, it offers a detailed examination of each pathway and a synopsis of the approved or in-development targeted therapies. In conclusion, finding the activated signaling pathways is crucial for developing effective treatment plans to improve the prognosis of patients with relapsed or refractory lymphoma. Trial Registration: ClinicalTrials.gov identifier: NCT02180724, NCT02029443, NCT02477696, NCT03836261, NCT02343120, NCT04440059, NCT01882803, NCT01258998, NCT01742988, NCT02055820, NCT02285062, NCT01855750, NCT03422679, NCT01897571.

Introduction: In Cameroon, screening and diagnosis of minor hemorrhagic syndromes remain difficult and few research studies have been done to assess the magnitude of future bleeding risk and the burden of these disorders on quality of life. Epistaxis and menorrhagia are the two leading causes of bleeding disorders in the world population.

Aim: The aim of this study was to investigate the biological abnormalities of hemostasis in patients with epistaxis and menorrhagia.

Method: From January to December 2021, we conducted a cross-sectional study in six hospitals with a gynecology and ENT department. We selected patients who presented epistasis or menorrhagia through clinical file and made them pass an interview and biological exams. Venous blood collected on EDTA tube allowed us to measure full blood count, thin blood smear, and blood grouping. PT, APPT, and fibrinogen assay were measured from citrate platelet-poor plasma. This plasma stored at -20°C for a maximum of 3 months allowed us to measure vWF : Ag and vWF : CBA ELISA. The bleeding time was measured at the time of sampling.

Result: In total, our study population consisted of 60 patients aged 01-45 years. Epistaxis (40%) and menorrhagia (29%) were the two main causes of bleeding complaints in our study, in addition to gingivorrhagia (15%) and prolonged bleeding after injury (03%). Almost 60% of the population had at least one abnormal hemostasis parameter. The main abnormalities found were low von Willebrand factor (30.19%), presence of macroplatelets (16.98%), prolonged bleeding time (15.09%), prolonged PT (15.09%), and low platelet count (¬07.55%).

Conclusion: In Cameroon, bleeding disorders manifested by epistaxis and menorrhagia are mainly caused by abnormalities of primary hemostasis.

Pregnant women and individuals with sickle cell trait (SCT) and underlying comorbidities are both independently more vulnerable to severe illness from coronavirus disease 2019 (COVID-19) compared to nonpregnant women and those without SCT. However, our understanding of the specific factors influencing susceptibility to COVID-19 infection among pregnant women with SCT is currently constrained by limited available data. This study aims to determine the risk and protective factors that influence the likelihood of COVID-19 infection in this population. A retrospective analysis was done among 151 women with SCT in the reproductive age group. Multivariable analysis was performed to determine the various factors affecting COVID-19 infection among pregnant women with SCT. The study found that COVID-19-vaccinated pregnant women with SCT had a 90% lower risk of contracting COVID-19 and were 9 times more likely to have a COVID-19 infection if they had a history of pulmonary conditions such as asthma or chronic obstructive pulmonary disease. The present study further emphasizes the importance of the COVID-19 vaccine in preventing infection and safeguarding the health of pregnant women with SCT, particularly those with underlying comorbidities.

Sickle cell disease (SCD) is a common genetic disorder with potentially serious sequelae that can be effectively treated with hydroxyurea. Despite its favorable benefit-risk profile, hydroxyurea uptake in patients with SCD is low. A pilot study was conducted at the Southern Alberta Rare Blood and Bleeding Disorders (SARBBDs) Comprehensive Care Program between January 2020 and September 2023 to assess the implementation of a pharmacist-led protocol for supporting the uptake of hydroxyurea among eligible patients with SCD and optimizing its dosing. The protocol standardized the prescription, monitoring, dose titration, and patient counselling by a clinic pharmacist. The number of patients enrolled in the SARBBDs program increased from 98 in January 2020 to 168 in 2023. During this period, the proportion of patients on hydroxyurea increased from 37.8% to 62.5%, the proportion of patients on hydroxyurea who were at a maximum tolerated dose (MTD) increased from 35.1% to 63.8%, and the average hemoglobin F level increased from 13.9% to 19.7%. The mean time to reach MTD was 10 months and required eight pharmacist interventions, six laboratory assessments, and three dose increases. Hydroxyurea continuation rates were high, with most discontinuations resulting from loss to follow-up or transition to a transfusion management strategy. This real-world pilot study demonstrated that implementation of a pharmacist-led prescribing and monitoring protocol nearly doubled hydroxyurea uptake and achievement of MTD in patients with SCD managed in a rare blood disorders clinic.